Swainsonine: an inhibitor of glycoprotein processing.
Swainsonine, an indolizidine alkaloid, inhibits the processing of asparagine-linked glycoproteins in both cell-free extracts and animal cells in culture. Thus, in a liver particulate enzyme preparation, swainsonine at 0.1-1.0 microM inhibited the mannosidase that releases [3H]mannose from a high mannose glycopeptide but only slightly inhibited the release of glucose from a glucose-labeled glycopeptide. MDCK and Chinese hamster ovary cells in culture incorporate [2-3H]mannose and [6-3H]glucosamine into both high mannose and complex types of oligosaccharides. When these cells were incubated with swainsonine and then labeled with mannose or glucosamine, there was a dramatic decrease in the amount of label in the complex type of glycopeptide and a substantial increase in the radioactivity in the high mannose type. This change was monitored by the increase in radioactivity that became susceptible to digestion by endoglucosaminidase H with increasing concentrations of swainosine. The endoglucosaminidase H-released oligosaccharide(s) from swainsonine-treated cells was larger and more homogeneous than that from controls and eluted from Bio-Gel P-4 at the position of Man9GlcNAc. Several tissue culture cell lines were grown in the presence of swainsonine to determine its effect on cell surface glycoproteins. Cells grown in the alkaloid showed an increased capacity to bind Escherichia coli B886, a bacterium that binds to high mannose glycoproteins. These cells also showed an increasing binding of [3H]concanavalin A.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D006224:Cricetinae; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins / Q000096:biosynthesis*; D010944:Plants; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011952:Receptors, Concanavalin A / Q000187:drug effects; D013329:Structure-Activity Relationship; D017026:Swainsonine
D000470:Alkaloids; D006023:Glycoproteins; D008565:Membrane Proteins; D011498:Protein Precursors; D011952:Receptors, Concanavalin A; D008361:Mannosidases; D017026:Swainsonine